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Vasoconstrictor effects of 8-iso-prostaglandin E2and 8-iso-prostaglandin F2αon human umbilical vein

Authors
Journal
European Journal of Pharmacology
0014-2999
Publisher
Elsevier
Publication Date
Volume
499
Identifiers
DOI: 10.1016/j.ejphar.2004.07.100
Keywords
  • Human Umbilical Vein
  • Isoprostane
  • Prostanoid Tp Receptor
  • Vasoconstriction
Disciplines
  • Biology
  • Pharmacology

Abstract

Abstract The present study was undertaken to determine whether 8-iso-prostaglandin E 2 and 8-iso-prostaglandin F 2α posses contractile action on human umbilical vein and to evaluate the possible involvement of prostanoid TP receptors in this effect. Human umbilical vein rings were mounted in organ baths and concentration–response curves to 8-iso-prostaglandin E 2 or 8-iso-prostaglandin F 2α were constructed. Both isoprostanes evoked concentration-dependent contraction. 8-iso-prostaglandin E 2 (pEC 50=6.90±0.03) was significantly more potent than 8-iso-prostaglandin F 2α (pEC 50=6.10±0.04). However, both isoprostanes were equieffective. The prostanoid TP receptor antagonists, ICI-192,605 (4-( Z)-6-(2- o-Chlorophenyl-4- o-hydroxyphenyl-1,3-dioxan- cis-5-yl)hexenoic acid) and SQ-29548 (7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1]hept-2-yl]-[1 S(1α,2α( Z),3α,4α)]-5-Heptenoic acid) produced a competitive rightward shift of 8-iso-prostaglandin E 2 concentration–response curves with p K B values of 8.91±0.04 and 8.07±0.07, respectively. When ICI-192,605 (1 nM) and SQ-29548 (10 nM) were evaluated against 8-iso-prostaglandin F 2α they produced a parallel rightward displacement of 8-iso-prostaglandin F 2α concentration–response curves without affecting the maximum responses giving p A 2 values of 9.02±0.12 and 8.26±0.13, respectively. In conclusion, the present study describes for the first time the vasoconstrictor action of 8-iso-prostaglandin E 2 and 8-iso-prostaglandin F 2α in human umbilical vein. Furthermore, the affinity values obtained with ICI-192,605 and SQ-29548 provide strong pharmacological evidence of prostanoid TP receptors involvement in this effect.

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